Ca/calmodulin-dependent protein kinase II α (CaMKIIα) signaling in the brain plays a critical role in regulating neuronal Ca homeostasis. Its dysfunctional activity is associated with various neurological and neurodegenerative disorders, including Parkinson's disease (PD). Using computational modeling analysis, we predicted that, two essential cysteine residues contained in CaMKIIα, Cys30 and Cys289, may undergo redox modifications impacting the proper functioning of the CaMKIIα docking site for Ca/CaM, thus impeding the formation of the CaMKIIα:Ca/CaM complex, essential for a proper modulation of CaMKIIα kinase activity. Our subsequent in vitro investigations confirmed the computational predictions, specifically implicating Cys30 and Cys289 residues in impairing CaMKIIα:Ca/CaM interaction. We observed CaMKIIα:Ca/CaM complex disruption in dopamine (DA) nigrostriatal neurons of post-mortem Parkinson's disease (PD) patients' specimens, addressing the high relevance of this event in the disease. CaMKIIα:Ca/CaM complex disruption was also observed in both in vitro and in vivo rotenone models of PD, where this phenomenon was associated with CaMKIIα kinase hyperactivity. Moreover, we observed that, NADPH oxidase 2 (NOX2), a major enzymatic generator of superoxide anion (O) and hydrogen peroxide (HO) in the brain with implications in PD pathogenesis, is responsible for CaMKIIα:Ca/CaM complex disruption associated to a stable CaCAM-independent CaMKIIα kinase activity and intracellular Ca accumulation. The present study highlights the importance of oxidative stress, in disturbing the delicate balance of CaMKIIα signaling in calcium dysregulation, offering novel insights into PD pathogenesis.
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http://dx.doi.org/10.1016/j.redox.2024.103254 | DOI Listing |
Sci Rep
December 2024
State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210009, China.
The diagnostic and prognostic value of quantitative electroencephalogram (qEEG) in the the onset of postoperative delirium (POD) remains an area of inquiry. We aim to determine whether qEEG could assist in the diagnosis of early POD in cardiac surgery patients. We prospectively studied a cohort of cardiac surgery patients undergoing qEEG for evaluation of altered mental status.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Clinical Pathobiology and Immunological Testing, School of Medical Laboratory, Qilu Medical University, Zibo 255300, China.
Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) are pluripotent stem cells derived from pre-implantation and post-implantation embryos, respectively. These cells are capable of interconversion through manipulation of key transcription factors and signaling pathways. While BAF chromatin remodeling complexes are known to play crucial roles in ESC self-renewal and pluripotency, their roles in EpiSCs and their interconversion with ESCs remain unclear.
View Article and Find Full Text PDFDent J (Basel)
December 2024
Department of Oral and Maxillofacial Sciences, School of Dentistry, Sapienza University of Rome, 00161 Rome, Italy.
Mandibular molar distalization is a complex orthodontic movement due to anatomic and biomechanical limitations. The opportunity to use a custom-made appliance with skeletal anchorage should be an advantageous alternative to traditional solutions: multiple extractions, interproximal reductions, vestibular inclination of incisal group. : A 14-year-old female patient with Class II malocclusion and ectopic upper and lower canines was treated in the lower arch with a custom-made appliance anchored on a mini-screw in the right buccal-shelf where the ectopy and crowding was severe.
View Article and Find Full Text PDFFASEB J
December 2024
Antibody and Vaccine Group, Faculty of Medicine, Centre for Cancer Immunology, School of Cancer Sciences, University of Southampton, Southampton, UK.
Osteosarcoma is the most common primary bone cancer, occurring frequently in children and young adults. Patients are treated with surgery and multi-agent chemotherapy, and despite the introduction of mifamurtide in 2011, there has been little improvement in survival for decades. 3-dimensional models offer the potential to understand the complexity of the osteosarcoma tumor microenvironment and aid in developing new treatment approaches.
View Article and Find Full Text PDFRSC Chem Biol
December 2024
School of Chemistry and Chemical Engineering, University of South China Hengyang 421001 China +86-743-8578079.
Androglobin (Adgb) was discovered as the fifth mammalian globin, but its structure and function remain elusive. In this study, the heme-binding globin domain of Adgb was expressed and its interaction with calmodulin (CaM) was investigated. The protein structure of Adgb and its complex with CaM were predicted using AlphaFold3 and HDOCK.
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